儿童肢体骨肉瘤患者的多中心回顾性临床预后分析

A multi-center retrospective analysis of clinical prognosis in children with extremity osteosarcoma

目的探讨影响儿童肢体骨肉瘤患儿(≤14岁)临床预后的相关因素。方法回顾性分析2000年6月至2017年10月国内7家骨肿瘤治疗中心收治的14岁以下肢体骨肉瘤患儿的病历资料,记录其一般资料、外科分期、术前有无穿刺活检、化疗方案、化疗次数、手术方式、复发转移及生存预后情况,应用Kaplan-Meier法描绘生存曲线并计算生存率,应用Log-rank检验进行单因素生存预后分析,应用Cox回归模型进行多因素的生存预后分析。结果肢体骨肉瘤患儿共147例,男73例,女74例。肢体骨肉瘤患儿的3、5年总生存率分别为65%、53%,中位总生存时间103个月(95%CI:92.8~128.5),3、5年的无瘤生存率分别为46%、38%,中位无瘤生存时间为33个月(95%CI:71.9~104.3)。膝关节周围:123例,膝关节以外:24例。Enneking外科分期:Ⅱ期139例,Ⅲ期8例。其中应用保肢术128例,截肢术19例。规范化疗组78例,非规范化疗组69例,规范化疗组与非规范化疗组5年总生存率分别为62%、43.8%;5年无瘤生存率分别为50.2%、31.6%。无复发转移的有75例,单纯复发13例,单纯转移41例,多发转移(包括复发伴转移)18例,其5年总生存率分别为88%、51.3%、21.4%、0。单因素分析结果显示:规范化疗、Enneking外科分期、术后辅助化疗次数和复发转移是影响肢体骨肉瘤患儿生存预后的相关因素(P<0.05);而性别、部位、手术方式及化疗方案中是否应用甲氨蝶呤(MTX)不是影响患儿生存预后的相关因素(P>0.05)。Cox回归多因素分析结果显示:规范化疗和复发转移是影响肢体骨肉瘤患儿生存预后的独立因素。结论规范的进行辅助化疗、有效的控制复发和转移可以提高肢体骨肉瘤患儿(≤14岁)的生存率,改善患儿的预后,化疗的不规范及复发转移严重影响患儿的预后。

Objective To explore the relevant influencing factors of clinical prognosis of children aged≤14 years with extremity osteosarcoma.Methods A retrospective analysis was performed for medical records of children aged≤14 years with extremity osteosarcoma admitted into seven bone cancer treatment centers in China from June 2000 to October 2017.The general data,surgical stage,preoperative biopsy,regimen/number of chemotherapy,surgical approach,recurrence,metastasis and survival prognosis were recorded.A Kaplan-Meier method was employed for plotting survival curve and calculating survival rate.A log-rank analysis was performed for determining the prognostic factors related to survival rate.And Cox model multivariate analysis was employed for identifying independent prognostic factors.Results There were 73 boys and 74 girls.They had a 3-and 5-year overall survival rates of 65%and 53%,with a median overall survival of 103 months(95%CI:92.8 to 128.5),a 3/5-year disease-free survival rates of 46%and 38%and a median disease-free survival of 33 months(95%CI:71.9 to 104.3).They were around knee joint(n=123)and outside knee joint(n=24).The Enneking surgical stage wasⅡ(n=139)andⅢ(n=8).There were extremity salvage(n=128)and amputation(n=19).The chemotherapy was standard(n=78)and non-standard(n=69).The 5-year overall survival rates of standard and non-standard chemotherapy groups were 62%and 43.8%respectively.The 5-year disease-free survival rates were 50.2%and 31.6%respectively.There were no recurrence or metastasis(n=75),simple recurrence(n=13),simple metastasis(n=41)and multiple metastases(n=18,including recurrence&metastasis).The 5-year overall survival rate was 88%,51.3%,21.4%and 0 respectively.Univariate analysis showed that standard chemotherapy,Enneking surgical stage,frequency of postoperative adjuvant chemotherapy,recurrence and metastasis were the relevant influencing factors of survival and prognosis of children with extremity osteosarcoma(P<0.05).However,gender,location,surgical approach and whether or not using methotrexate(MTX)in chemotherapy regimen were not the relevant influencing factors of survival and prognosis(P>0.05).Cox regression multivariate analysis showed that standard chemotherapy,recurrence and metastasis were independent influencing factors of survival and prognosis of children with extremity osteosarcoma(P<0.05).Conclusions Standard neoadjuvant chemotherapy and effective control of recurrence and metastasis can improve the survival rate and prognosis of children with extremity osteosarcoma.Non-standard chemotherapy.Recurrence and metastasis adversely affect the prognosis of patients.